Expert Anticipates Cure in Acute Lymphoblastic Leukemia

With positive results from agents such as inotuzumab ozogamicin (Besponsa), ponatinib (Iclusig), blinatumomab (Blincyto), tisagenlecleucel (Kymriah), and pembrolizumab (Keytruda), Elias Jabbour, MD, said he believes acute lymphoblastic leukemia (ALL) will be cured sooner rather than later.

“The cure of ALL is going to happen in our lifetime,” said Jabbour, an associate professor of Medicine in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. “These drugs are very promising. The future is to use these drugs, and immunotherapy, in a frontline setting to eradicate minimal disease and increase the cure rate from 40%, to 50%, to 80%.”

In an interview with OncLive®, Jabbour discussed recent clinical trial results in ALL, the role of immunotherapy, and the biggest challenges facing the field.

OncLive: What is the current treatment landscape in ALL?

Jabbour: There are a lot of developments happening today in ALL. We are improving the outcome of this disease. In frontline pediatric ALL, the cure rate is 80% to 90%. The outcome is still not as good in adult ALL, with a cure rate approaching 50%. That has to do with the biology of the disease—it is quite different between pediatric and adult.

With the progress being made in ALL today, we're able to personalize our frontline therapies. [There is] success encountered with tyrosine kinase inhibitors in combination with chemotherapy for FLT3-positive ALL. Today, with ponatinib in combination with chemotherapy, we're approaching a 5-year survival rate of 70% to 75% without the need for transplantation, which is major progress.

The addition of monoclonal antibodies, starting with rituximab (Rituxan), to chemotherapy has shown improvement in survival. For Burkitt disease and precursor B-cell ALL, we have new drugs; among them is the bispecific monoclonal antibody blinatumomab that was approved for relapsed/refractory ALL and [now] for minimal residual disease (MRD)-positive disease as of [March] 2018. We have inotuzumab ozogamicin, which is an anti-CD22 drug conjugated to ozogamicin, which has shown activity in relapsed/refractory disease with improvement in overall survival (OS).

Recently, we had the chimeric antigen receptor (CAR) T cells approved, which harness the immune system of the patients to target the B-cell marker CD19. We've seen good results in a phase II study that led to FDA approval of the drug for patients up to the age of 25 who failed multiple lines of therapy.

There are a lot of things happening today in ALL. The question is, “How can we move these drugs into the frontline setting in order to further improve outcomes, eliminate the need for chemotherapy and intensive chemotherapy, and for further improvement of OS?”

What is the role of immunotherapy in this setting?

One of the novelties in cancer and in ALL is immunotherapy. We try to go after specific targets and spare the normal organs.

Rituximab, by itself, does not work. When you combine rituximab plus chemotherapy, regardless of what chemotherapy backbone you use, you have an improvement in survival outcome. That has become standard of care.

Then we have the CD19 bispecific T-cell engagers. Blinatumomab is the first on that list; the drug was first [applied] in patients with minimal or measurable disease, and later on was taken to the relapsed/refractory setting in 189 patients in a phase II trial that led to approval of the drug with a response rate of 44%.

Later on, there was the randomized TOWER trial where patients who were Philadelphia chromosome–negative failed multiple lines of therapy and were randomized to standard of care or blinatumomab. There was an improvement in response rate and, among responders who had deeper molecular responses, an improvement in OS of 7.7 months compared with 4 months. We had better response in patients who received blinatumomab as the first salvage compared with second salvage and beyond.

In addition, the drug was explored in a larger scale in patients in Europe with minimal disease. In a trial called BLAST, 116 patients were treated. Eighty percent was the complete MRD response rate, and among responders, we saw an improvement in OS and progression-free survival (PFS) compared with patients who did not respond. Based on these findings, the drug was approved by the FDA.